Evidence for an ancient BRCA1 pathogenic variant in inherited breast cancer patients from Senegal
Rokhaya Ndiaye, Jean Pascal Demba Diop, Violaine Bourdon-Huguenin, Ahmadou Dem, Doudou Diouf, Mamadou Moustapha Dieng, Pape Saloum Diop, Serigne M. Gueye, Seydi Abdoul Ba, Yacouba Dia, Sidy Ka, Babacar Mbengué, Alassane Thiam, Maguette Sylla Niang, Papa Madièye Guéye, Oumar Faye, Philomène Lopez Sall, Aynina Cissé, Papa Amadou Diop, Hagay Sobol, Alioune Dièye
Abstract
Abstract BRCA1 and BRCA2 are the most incriminated genes in inherited breast/ovarian cancers. Several pathogenic variants of these genes conferring genetic predisposition have been described in different populations but rarely in sub-Saharan Africa. The objectives of this study were to identify pathogenic variants of the BRCA genes involved in hereditary breast cancer in Senegal and to search for a founder effect. We recruited after free informed consent, 27 unrelated index cases diagnosed with breast cancer and each having a family history. Mutation screening of the genes identified a duplication of ten nucleotides c.815_824dupAGCCATGTGG, (p.Thr276Alafs) (NM_007294.3) located in exon 11 of BRCA1 gene, in 15 index cases (allelic frequency 27.7%). The pathogenic variant has been previously reported in African Americans as a founder mutation of West African origin. Haplotypes analysis of seven microsatellites surrounding the BRCA1 gene highlights a shared haplotype encompassing ~400 kb between D17S855 and D17S1325. This haplotype was not detected in none of 15 healthy controls. Estimation of the age of the pathogenic variant suggested that it occurred ~1400 years ago. Our study identified a founder pathogenic variant of BRCA1 predisposing to breast cancer and enabled the establishment of an affordable genetic test as a mean of prevention for Senegalese women at risk.